It is known that in mammals in general and particularly in man, synovial fluid acts to effectively lubricate the surfaces of bones that are in frictional contact to form joints, as well as lubricating other physiological articulations such as muscles, tendons, ligaments, cartilage or bones which move relative to other muscles, ligaments, tendons, cartilage or bones. For example, the synovial fluid is able to provide effective lubrication in joints such as the human knee, where the standing applied load is about 3 kg/cm.sup.2.
As will be recognised, man and other mammals are susceptible to the widespread and debilitating effects of osteoarthritis and other rheumatic diseases. Osteoarthritis is considered to be a disorder characterised by "wear and tear" of a joint which has often been mechanically abused. It is inherent in osteoarthritis that the lubrication system of the joint is compromised which results in degeneration of the joint such that it then becomes painful to move, especially under load. In many instances, if the patient restricts or stops using that joint as a result of the inherent pain, the disease process is exacerbated due to the further reduction in joint lubrication by synovial fluids. Other disorders are also characterised by reduced lubrication of joints or other physiological articulations such as situations where muscle, ligament, tendon, cartilage or bone moves relative to other muscle, ligament, tendon, cartilage or bone. Such disorders are often associated with over use or injuries, particularly sporting injuries. It is therefore desirable to develop a lubricant composition and method of utilising such a composition to improve the lubrication of joints and other physiological articulations in order to keep the joint or articulation mobile and reduce mechanical stress which often results in pain especially during movement.
It is desirable that such a lubricant and methods of lubrication would reduce the co-efficient of friction between movable surfaces in order to facilitate release of surfaces and initiate motion, reduce wear of articular surfaces as well as, in the case of bone/cartilage, rendering the surfaces hydrophobic and therefore less permeable to fluid to prevent hydration of cartilage (it is commonly found that there is increased hydration of articular cartilage in arthritis).
International Patent Application No. PCT/AU88/00322 advocates the use of a lubricant which comprises a phospholipid in combination with hyaluronic acid and optionally further pharmaceutically acceptable excipients and/or additives. It is noted however, that problems are associated with this prior art composition and its method of use as a joint lubricant. Some of these problems are (a) that hyaluronic acid is extracted and purified from birds, animals and other living organisms and for this reason it can include impurities which may result in an immunogenic or pyrogenic response; (b) hyaluronic acid per se initiates an appreciable inflammatory reaction in animal tissues; (c) there are limits to the capability of hyaluronic acid to carry phospholipids in reversible chemical association such that in order to introduce sufficient phospholipid levels into an animal joint or articulation in order to improve lubrication under load, it is necessary to administer a relatively large dose of the phospholipid/hyaluronic acid composition.
International Patent Publication No. PCT/AU91/00063 by the same applicants as the present application proposed an artificial tear composition comprising a phospholipid and optionally hyaluronic acid or a physiologically suitable salt thereof, in an opthalmically suitable carrier. It was disclosed that one possible carrier was propylene glycol. It was not considered at the time, however, that such a composition could be utilised for lubrication of animal joints or other physiological articulations (as defined herein).
It was also considered that the composition referred to in PCT/AU91/00063 would not be appropriate for lubrication of animal joints due to the fact that phospholipid would not be suitably miscible with propylene glycol. Further, it would be anticipated that as phospholipid is highly insoluble in water, that when a solution of phospholipid and a solvent is diluted with water the phospholipid would precipitate in granular form and would be ineffective as a lubricant. Unexpectedly however, it has been found that propylene glycol is totally miscible with phospholipids, such as Dipalmitoyl phosphatidylcholine (DPPC), at all concentrations, so that it is possible to prepare solutions of phospholipid in propylene glycol of concentrations up to 1 g phospholipid per ml of propylene glycol. This compares most favourably with the maximum concentration of phospholipid/hyaluronic acid mixtures of 200 mg phospholipid per 1 ml hyaluronic acid. It was also unexpectedly found that when administered within a joint, and thereby in contact with aqueous synovial fluid, there was no evidence of floccular precipitation and the articular surfaces became exceptionally slippery.
In addition it has been found that when propylene glycol is administered in association with phospholipid that the phospholipid ameliorates any minor inflammatory response which may result from the propylene glycol such that there is overall either no or only a minor and insignificant inflammatory response elicited.
Furthermore, mixtures of phospholipid and propylene glycol are heat stable so that they can be autoclaved to effect sterilisation. It is also noted that propylene glycol is manufactured synthetically and thereby substantially eliminates the possibility of immunogenic or pyrogenic materials being included within a composition administered to an animal.
Accordingly, it is an object of the present invention to provide methods of lubrication of mammalian joints and other physiological articulations (as defined herein). It is a further object of the present invention to at least substantially overcome the problems associated with the prior art lubrication methods, as mentioned herein. Other objects of this invention will become apparent from the following description thereof.